A potassium ion-dependent RNA structural switch regulates human pre-miRNA 92b maturation

Area of Science:

• Molecular Biology
• RNA Biology
• Bioinformatics

Background:

• MicroRNAs (miRNAs) are key regulators of gene expression.
• miRNA biogenesis critically depends on Dicer-mediated cleavage of precursor miRNAs (pre-miRNAs).
• The canonical structure of pre-miRNAs is a stem-loop, targeted by Dicer.

Purpose of the Study:

• To investigate the role of G-quadruplex (GQ) structures in pre-miRNA maturation.
• To explore GQ formation as an alternative structure to the stem-loop in pre-miRNAs.
• To determine the impact of GQ formation on Dicer cleavage and miRNA biogenesis.

Main Methods:

• Bioinformatics analysis to identify putative GQ-forming sequences in pre-miRNAs.
• In vitro and in vivo experiments to study pre-miRNA 92b structure and Dicer interaction.
• Analysis of potassium ion (K+) dependency on RNA structure and Dicer cleavage.

Main Results:

• Approximately 16% of pre-miRNAs contain putative GQ-forming sequences.
• A G-quadruplex (GQ) structure was identified in human pre-miRNA 92b, alternative to the stem-loop.
• GQ formation in pre-miRNA 92b conferred resistance to Dicer-mediated cleavage.
• A K+-ion-dependent equilibrium between GQ and stem-loop structures regulates pre-miRNA 92b maturation.

Conclusions:

• G-quadruplex formation represents a novel structural alternative to the canonical stem-loop in pre-miRNAs.
• GQ formation in pre-miRNA 92b inhibits Dicer processing, affecting mature miRNA levels.
• This structural regulation impacts target gene silencing, revealing a new layer of miRNA biogenesis control.